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1. National Institute on Aging
National Institutes of Health
ALZHEIMER’S DISEASE
UnravelingtheMystery

2. The Impact of AD
Once considered a rare disorder,
Alzheimer’s disease is now seen as a
major public health problem that is
seriously affecting millions of older
Americans and their families.
The Federal government’s lead agency for Alzheimer’s
disease research is the National Institute on Aging, part of
the National Institutes of Health. NIH is part of the U.S.
Department of Health and Human Services.
Slide 2

3. Alzheimer’s Disease: Unraveling the Mystery
• What is AD? (slides 4 – 6)
• Inside the Human Brain (slides 8 – 14)
• AD and the Brain (slides 16 – 22)
• AD Research: Finding New Answers and Asking Better
Questions (slides 24 – 35)
• Improving Support for Families and Other Caregivers
(slides 37 – 39)
• Where to Get Help (slides 40-41)
Slide 3

4. What is AD?
Alzheimer’s disease is an
irreversible, progressive brain
disease that slowly destroys
memory and thinking skills.
Although the risk of developing AD increases with age – in
most people with AD, symptoms first appear after age 60 –
AD is not a part of normal aging. It is caused by a fatal
disease that affects the brain.
Slide 4

5. What is AD?
AD Statistics….
• AD is the most common
cause of dementia among
people age 65 and older.
• Scientists estimate that
around 4.5 million people
now have AD. • By 2050, 13.2 million older
• For every 5-year age Americans are expected to have
group beyond 65, the AD if the current numbers hold
percentage of people with
AD doubles. and no preventive treatments
become available.
Slide 5

6. What is AD?
Where are people with AD cared for?
• home
• assisted living facilities (those in
the early stages)
• nursing homes (special care units)
• The national cost of caring for
people with AD is about $100
billion every year.
Slide 6

7. Inside the Human Brain
• The Brain’s Vital Statistics (slide 8)
• The Three Main Players (slides 9 – 11)
• Other Crucial Parts (slide 12)
• The Brain in Action (slide 13)
• Neurons (slide 14)
Slide 7

8. Inside the
Human Brain
To understand
Alzheimer’s disease,
it’s important to
know a bit about the
brain…
The Brain’s Vital Statistics
• Adult weight:
about 3 pounds
• Adult size:
a medium cauliflower
• Number of neurons:
100,000,000,000
(100 billion)
• Number of synapses
(the gap between neurons):
100,000,000,000,000
(100 trillion)
Slide 8

9. Inside the Human Brain
The Three Main Players
1. Cerebral Hemispheres – where sensory information received from the
outside world is processed; this part of the brain controls voluntary
movement and regulates conscious thought and mental activity:
• accounts for 85% of brain’s weight
• consists of two hemispheres connected by the corpus callosum
• is covered by an outer layer called the cerebral cortex
Slide 9

10. Inside the Human Brain
The Three Main Players
2. Cerebellum – in charge of balance and coordination:
• takes up about 10% of brain
• consists of two hemispheres
• receives information from eyes, ears, and muscles and joints
about body’s movements and position
Slide 10

11. Inside the Human Brain
The Three Main Players
3. Brain Stem – connects the spinal cord with the brain
• relays and receives messages to and from muscles, skin, and
other organs
• controls automatic functions such as heart rate, blood pressure,
and breathing
Slide 11

12. Inside the Human Brain
Other Crucial Parts
• Hippocampus: where short-term memories are converted to
long-term memories
• Thalamus: receives sensory and limbic information and
sends to cerebral cortex
• Hypothalamus: monitors certain activities and controls
body’s internal clock
• Limbic system: controls emotions and instinctive behavior
(includes the hippocampus and parts of the cortex)
Slide 12

13. Inside the Human Brain
The Brain in Action
Hearing Words Speaking Words Seeing Words Thinking about Words
Different mental activities take place in different parts of the
brain. Positron emission tomography (PET) scans can measure
this activity. Chemicals tagged with a tracer “light up” activated
regions shown in red and yellow.
Slide 13

14. Inside the
Human Brain
Neurons
• The brain has billions of
neurons, each with an axon
and many dendrites.
• To stay healthy, neurons
must communicate with
each other, carry out
metabolism, and repair
themselves.
• AD disrupts all three of
these essential jobs.
Slide 14

15. AD and the Brain
• Plaques and Tangles (slides 16 – 18)
• The Changing Brain in AD (slides 19 – 22)
Slide 15

16. AD and the Brain
Plaques and Tangles: The Hallmarks of AD
The brains of people with AD have an abundance of two
abnormal structures:
• beta-amyloid plaques, which are dense deposits of protein and
cellular material that accumulate outside and around nerve
cells
• neurofibrillary tangles, which are twisted fibers that build up
inside the nerve cell
An actual AD plaque An actual AD tangle
Slide 16

17. AD and the Brain
Beta-amyloid Plaques
1. Amyloid precursor protein (APP) is the
precursor to amyloid plaque.
1. APP sticks through the neuron
membrane.
2. Enzymes cut the APP into fragments
of protein, including beta-amyloid.
2.
3. Beta-amyloid fragments come together
in clumps to form plaques.
In AD, many of these clumps form,
disrupting the work of neurons. This
3. affects the hippocampus and other areas
of the cerebral cortex.
Slide 17

18. AD and the Brain
Neurofibrillary
Tangles
Neurons have an internal support structure partly made up of
microtubules. A protein called tau helps stabilize microtubules. In AD,
tau changes, causing microtubules to collapse, and tau proteins clump
together to form neurofibrillary tangles. Slide 18

19. AD and the Brain
The Changing Brain in
Alzheimer’s Disease
No one knows what causes AD to begin,
but we do know a lot about what happens
in the brain once AD takes hold.
Pet Scan of
Normal Brain
Pet Scan of Alzheimer’s
Disease Brain
Slide 19

20. AD and the Brain
Preclinical AD • Signs of AD are first noticed in
the entorhinal cortex, then
proceed to the hippocampus.
• Affected regions begin to shrink
as nerve cells die.
• Changes can begin 10-20 years
before symptoms appear.
• Memory loss is the first sign of
AD.
Slide 20

21. AD and the Brain
• AD spreads through the brain. The
Mild to Moderate AD cerebral cortex begins to shrink as
more and more neurons stop
working and die.
• Mild AD signs can include memory
loss, confusion, trouble handling
money, poor judgment, mood
changes, and increased anxiety.
• Moderate AD signs can include
increased memory loss and
confusion, problems recognizing
people, difficulty with language
and thoughts, restlessness,
agitation, wandering, and repetitive
statements.
Slide 21

22. AD and the Brain
Severe AD
• In severe AD, extreme shrinkage
occurs in the brain. Patients are
completely dependent on others for
care.
• Symptoms can include weight loss,
seizures, skin infections, groaning,
moaning, or grunting, increased
sleeping, loss of bladder and bowel
control.
• Death usually occurs from
aspiration pneumonia or other
infections. Caregivers can turn to a
hospice for help and palliative care.
Slide 22

23. AD Research: Finding New Answers
and Asking Better Questions
• The Search for Causes (slides 24 – 28 )
• Diagnosing AD (slides 29 – 30)
• Clinical Trials (slide 31)
• The Search for Treatments (slides 32-33)
• New NIA Study (slide 34)
• Managing the Symptoms of AD (slide 35)
Slide 23

24. AD Research: the
Search for Causes
AD develops
• AD develops when genetic, lifestyle, and environmental
factors work together to cause the disease process to start.
• In recent years, scientists have discovered genetic links to
AD. They are also investigating other factors that may
play a role in causing AD. NIA-funded Alzheimer’s
Disease Centers (ADCs) across the country are leading
the research efforts looking into causes, diagnosis, and
treatment of AD.
Slide 24

25. AD Research: the Search for Causes
Genetic Studies
The two main types of AD are
early-onset and late-onset:
• Early-onset AD is rare, usually
affecting people aged 30 to 60
and usually running in families.
Researchers have identified
mutations in three genes that
cause early-onset AD.
• Late-onset AD is more
common. It usually affects
people over age 65.
Researchers a gene that produces a protein called apolipoprotein E (ApoE).
have identified
Scientists believe this protein is involved in the formation of beta-amyloid
plaques.
Slide 25

26. AD Research: the Search for Causes
Late-onset AD
Genetics Study
• Partnership between the NIA and the
Alzheimer’s Association
• Need to recruit a total of 1,000 families to
find the remaining late-onset risk factor
genes
• 2 or more living siblings with AD
• One other living family member with or
without AD
• Contact: e-mail: alzstudy@iupui.edu or
Website: www.ncrad.org
Slide 26

27. AD Research: the Search for Causes
Studies at the Cellular and
Molecular Level
• Oxidative damage from free
radical molecules can injure
neurons.
• Homocysteine, an amino acid, is a risk factor for heart disease. A study
shows that an elevated level of homocysteine is associated with
increased risk of AD.
• Scientists are also looking at inflammation in certain regions of the
brain and strokes as risk factors for AD.
Slide 27

28. AD Research: the Search for Causes
Epidemiologic Studies
Scientists examine characteristics, lifestyles, and disease
rates of groups of people to gather clues about possible
causes of AD. The NIA is currently funding epidemiologic
studies in a variety of different groups. Two of the studies
focus on religious communities. Researchers conduct
yearly exams of physical and mental status, and studies of
donated brains at autopsy. Some early results indicate:
• Mentally stimulating activity protects the brain in some
ways.
• In early life, higher skills in grammar and density of ideas
are associated with protection against AD in late life.
Slide 28

29. AD Research: Diagnosing AD
Experienced physicians in specialized AD
centers can now diagnose AD with up to 90
percent accuracy. Early diagnosis has
advantages:
• Doctors can rule out other conditions
that may cause dementia.
• If it is AD, families have more time to
plan for the future.
• Treatments can start earlier, when they
may be more effective.
• It helps scientists learn more about the
causes and development of AD.
Slide 29

30. AD Research: Diagnosing AD
Physicians today use a number
of tools to diagnose AD:
• a detailed patient history
• information from family and
friends
• physical and neurological
exams and lab tests
• neuropsychological tests
• imaging tools such as CT scan,
or magnetic resonance imaging
(MRI). PET scans are used
primarily for research purposes
Slide 30

31. AD Research: Clinical Trials
Clinical trials are the primary way
that researchers find out if a
promising treatment is safe and
effective.
• Trials examine approved drugs
to see if they can be used for
other purposes, or look at
experimental drugs.
• Participating in a trial means
regular contact with the study
team, who can provide state-of-
the-art AD care.
Slide 31

32. AD Research: the Search for Treatments
Drugs used to treat mild to moderate AD symptoms include:
• Aricept
• Exelon
• Reminyl
An additional drug, Namenda, has been approved to treat symptoms of
moderate to severe AD. These drugs can help improve some patients’
abilities to carry out activities up to a year or so, but they do not stop or
reverse AD.
Scientists are also studying agents that someday may be
useful in preventing AD. For example, they have
experimented with a vaccine against AD. Although the
first clinical trial was stopped due to side effects in some
participants, valuable information was gathered.
Slide 32

33. AD Research: the Search for New Treatments
Researchers also are looking at other treatments,
including:
• cholesterol-lowering drugs called
statins
• anti-oxidants (vitamins) and folic acid
• anti-inflammatory drugs
• substances that prevent formation of
beta-amyloid plaques
• nerve growth factor to keep neurons
healthy
Slide 33

34. AD Research: New NIA Study
The NIA is launching a new research
partnership, called the Neuroimaging and
Biomarkers of AD Initiative, to study how
the brain changes in Mild Cognitive
Impairment (MCI) and AD.
• Using MRIs and PET scans conducted at
regular intervals, researchers hope to learn
precisely when and where in the brain
problems occur.
• Researchers will also examine blood samples
to check for higher levels of abnormal
substances that could be considered
“biomarkers” of AD.
Slide 34

35. AD Research: Managing Symptoms
Between 70 to 90% of people with AD eventually
develop behavioral symptoms, including sleeplessness,
wandering and pacing, aggression, agitation, anger,
depression, and hallucinations and delusions. Experts
suggest these general coping strategies for managing
difficult behaviors:
• Stay calm and be understanding.
• Be patient and flexible. Don’t argue or try to convince.
• Acknowledge requests and respond to them.
• Try not to take behaviors personally. Remember: it’s
the disease talking, not your loved one.
Experts encourage caregivers to try non-medical coping strategies
first. However, medical treatment is often available if the behavior
has become too difficult to handle. Researchers continue to look at
both non-medical and medical ways to help caregivers.
Slide 35

36. Improving Support for Families
and Other Caregivers
• Who are the AD Caregivers? (slide 37)
• Demands of Caregiving (slide 38)
• Technology and Caregiving (slide 39)
• National Support for Caregivers (slide 40)
• How to Contact the ADEAR Center (slide 41)
Slide 36

37. Support for Caregivers
Who are the AD Caregivers?
• Spouses – the largest group. Most are older with
their own health problems.
• Daughters – the second largest group. Called the
“sandwich generation,” many are married and
raising children of their own. Children may need
extra support if a parent’s attention is focused on
caregiving.
• Grandchildren – may become major helpers.
• Daughters-in-law – the third largest group.
• Sons – often focus on the financial, legal, and
business aspects of caregiving.
• Brothers and Sisters – many are older with
their own health problems.
• Other – friends, neighbors, members of the
faith community.
Slide 37

38. Support for Caregivers
Demands of Caregiving
AD takes a huge physical and
emotional toll. Caregivers must
deal with changes in a loved one’s
personality and provide constant
attention for years. Thus, caregivers
are especially vulnerable to
physical and emotional stress.
• Peer support programs can help link
caregivers with trained volunteers.
Other support programs can offer
services geared to caregivers dealing
with different stages of AD.
Slide 38

39. Support for Caregivers
Technology and Caregiving
The NIA is studying how computers
can provide information and support
to family caregivers through:
• computer-based bulletin boards
• chat rooms
• Q & A modules
• medical advice forums
These features have become very popular among users
because they reach many people at once, are private and
convenient, and are available around the clock.
Slide 39

40. National Support for Caregivers
Alzheimer’s Association
• Local chapters provide referrals to
area resources and services, and
sponsor the Safe Return Program,
support groups, and educational
programs:
1-800-272-3900
www.alz.org
Eldercare Locator
• Nationwide service of the Federal
Government helps caregivers
locate local support and resources:
1-800-677-1116
www.eldercare.gov
Slide 40

41. For more information on Alzheimer’s disease and a
list of the NIA-funded Alzheimer’s Disease Centers,
contact the Alzheimer’s Disease Education and
Referral (ADEAR) Center at:
1-800-438-4380
www.alzheimers.org
The ADEAR Center is a service of:
National Institute on Aging, part of the
National Institutes of Health (NIH), part of the
Department of Health and Human Services
This PowerPoint slideshow is based on the publication Alzheimer’s Disease:
Unraveling the Mystery. Contact the ADEAR Center for free copies.
Slide 41